Previous randomized, controlled clinical trials suggest that oral tetracyclines may reduce the symptoms of joint inflammation in rheumatoid arthritis (RA). This class of antibiotics has well-described antimicrobial effects as well anti-collagenase activity. Collagenase is an enzyme that degrades cartilage and bone and is believed to be important in the pathogenesis of RA. This study evaluates the safety and potential clinical efficacy of I.V. doxycycline therapy in 60 patients with RA and will explore whether any improvements in arthritis from the doxycycline are due to its antibacterial actions or ability to reduce the activity of collagenase. The three objectives of this study are: 1) To determine the feasibility, safety, and potential clinical efficacy of I.V. doxycycline therapy in RA and explore whether this agent ameliorates clinical manifestations of this disease by suppressing bacterial infection or matrix metalloproteinases (MMP) activity; 2) To determine whether daily and weekly treatment with I.V. doxycycline can reduce urinary excretion of collagen crosslinks in patients with RA and potentially retard joint damage; and 3) To explore the potential effects of daily and weekly I.V. doxycycline therapy on biochemical markers of cartilage proteoglycan degradation. There are three groups in which patients will be randomized: Group I receives I.V. doxycycline and oral placebo, Group II will receives I.V. placebo and oral azithromycin, and Group III receives I.V. and oral placebo. Each patient receives a peripheral-line catheter for the home infusion therapy which lasts 21 days. Weekly infusions are administered from week 4 through 11. Duration of the study is 36 weeks with a total of 6 visits including the baseline admission for insertion of the peripheral line catheter and first infusion of the study medication. Study enrollment, which began in April of 1995, includes ten patients thus far. Various ethnic backgrounds are represented in the present sample, such as African-American, Caucasian, and Native American. Overall patient response is unknown at this time due to the double-blind study design. However, patients appear to be doing well and there are no study-related adverse events to report. Recruitment will continue until a total of 60 patients have been enrolled.